Major emphasis wll be placed on the delineation of two new pathways of 1,25-(OH)2D3 and 25-OH-D3 metabolism which have been discovered in the past year. The resulting metabolites will be isolated and identified and the enzymes responsible will be studied. Major emphasis will also be placed on a study of the receptor proteins for 1,25-(OH)2D3 in intestine, bone and kidney. A third major area will be continued- chemical synthesis of analogs of 1,25-(OH)2D3 and their biological activities will be determined. Work on vitamin A will center on its role in the cell cycle of basal epithelial cells and its metabolism therein. The requirements of the in vitro prothrombin synthesis system and the vitamin K dependent carboxylase system will be defined in more detail. Attempts to solubilize the carboxylase system and resolve the various enzymatic activities will be initiated. The subcellular location of the carboxylase activity will be determined, and an attempt will be made to isolate a proposed higher molecular weight prothrombin precursor. Studies will continue on the nature and function of the selenium- containing moiety of glutathione peroxidase and investigations will be initiated on the biosynthesis of glutathione peroxidase. The relationships of vitamin E, selenium, sulfur-containing amino acids and unsaturated lipids to lipid peroxidation in vivo as measured by ethane production and to cataracts will continue to be pursued. Attempts will be made to elucidate the mechanisms whereby silver and tri-osthocresyl phosphate precipitate selenium-vitamin E responsive diseases.